The long term objective of this application is to understand and eventually improve the process by which the adult brain attempts to heal from a transient focal ischemic deficit. Stroke remains the major devastating disabler for the adult neurologic system. Our present research focus on the prevention of stroke needs to be balanced with studies that emphasize the process of repair and recovery after stroke. This study highlights the new finding that the adult brain develops neuroprogenitor cells in the hippocampus, which are stimulated in response to even a remote ischemic injury. The project emphasizes those factors which stimulate the proliferation of these progenitor cells. Later studies will examine the control of their survival, differentiation and migration. The specific aims of this proposal will emphasize in vivo models of proliferation in the rodent after transient cerebral ischemia. We will use a model of dentate gyrus cell proliferation and examine hypothesized growth factor effects and the mechanism of delivery of those effects from the infarct to a remote site. The second specific aim will analyze these cells themselves by in vitro culturing of the progenitor cells derived from both ischemic and non-ischemic animals. This model will test their susceptibility to growth factors. Growth factors will be further analyzed by microarray analysis and ELISA in the ischemic animals for increased production of the growth factors. Information from these studies will allow us to enhance this natural process of cell proliferation at the time of ischemia and lay the groundwork for stimulation of neuroplasticity after focal cerebral ischemia. [unreadable] [unreadable]